[1-12-2011] The U.S. Food and Drug Administration (FDA)
is updating the public about its ongoing safety review of Lantus
(insulin glargine) and a possible increased risk of cancer. Lantus
is a long-acting modified version of human insulin (insulin analog)
used to control blood sugar in patients with Type 1 and Type 2
diabetes.

In July 2009, FDA issued an Early Communication About Safety of Lantus (insulin
glargine) to inform the public that it was reviewing four
published observational studies, three of which suggested an
increased risk of cancer associated with the use of
Lantus.1-4 FDA has reviewed the four studies and has
determined that the evidence presented in the studies is
inconclusive, due to limitations in how the studies were designed
and carried out and in the data available for analysis. These
limitations prevent our ability to attribute the observed cancer
risk to Lantus (see Data
Summary below).

FDA has also reviewed results from a five-year randomized
clinical trial, Evaluation of Diabetic Retinopathy Progression
in Subjects with Type 2 Diabetes Mellitus Treated with Oral Agents
Plus Insulin, which compared Lantus to Neutral Protamine
Hagedorn (NPH) insulin in individuals with Type 2 diabetes. The
results did not show an increased risk of cancer in subjects
treated with Lantus compared to those treated with NPH insulin;
however, this study was not specifically designed to evaluate
cancer outcomes.

FDA is continuing to work with the manufacturer of Lantus and
the U.S. Department of Veterans Affairs (VA) to further evaluate
the long-term risk, if any, for cancer associated with the use of
Lantus.

At this time, FDA has not concluded that Lantus increases the
risk of cancer. Our review is ongoing, including review of
information from a current clinical trial, and the Agency will
update the public when it has additional information.

Healthcare professionals should continue to follow the
recommendations in the drug label when prescribing Lantus.

In July 2009, FDA issued an Early Communication About Safety of Lantus (insulin
glargine) to inform the public that it was reviewing four
published observational studies, three of which suggested an
increased risk of cancer associated with the use of
Lantus.1-4 FDA has completed its review of the studies
and has determined that the evidence presented in these studies is
inconclusive due to methodological limitations.

The duration of patient follow-up in all four studies was
shorter than what is generally considered necessary to evaluate
cancer risk from drug exposure. Also, the four studies provided
limited information on patients' use of insulin products.
Additionally, some of these studies did not take into account
whether the patients used any anti-diabetic drugs before the study
time period or whether there were any changes in how patients used
these drugs during the study period. Furthermore, risk factors for
cancer, such as smoking, family history of cancer, and obesity, may
not have been adequately controlled for in these studies. This
prevents our ability to attribute the observed cancer risk solely
to Lantus.

In addition to the four published observational studies, FDA has
reviewed results from the Evaluation of Diabetic Retinopathy
Progression in Subjects with Type 2 Diabetes Mellitus Treated with
Oral Agents Plus Insulin trial, which was a five-year,
randomized trial comparing Lantus to NPH insulin in individuals
with Type 2 diabetes. A post-hoc evaluation (examining the data
after the trial concluded for outcomes that were not identified a
priori) of the occurrence of cancer was conducted. The safety
population consisted of over 500 patients per treatment arm with a
median exposure of approximately five years. The overall occurrence
of all cancers was 5.8% in the Lantus arm versus 9.3% in the NPH
insulin arm. The odds ratio for all cancers was 0.60 (95%
Confidence Interval 0.36, 0.99). The results did not support an
increased risk of cancer associated with Lantus in comparison to
NPH insulin; however, the study was not designed or powered to
evaluate cancer outcomes and these outcomes were not verified in
medical records or reviewed by cancer experts.

FDA continues to work with the manufacturer of Lantus and other
scientists to further evaluate the safety of Lantus. The
manufacturer's ongoing Outcome Reduction with Initial Glargine
Intervention (ORIGIN) clinical trial has been amended to adjudicate
(have a panel of experts in cancer evaluate) all cases of cancer
occurring during the trial. The ORIGIN trial is designed to
determine if treatment with Lantus to reduce fasting plasma glucose
to 95 mg/dL or less would reduce the incidence of cardiovascular
events in patients with pre-diabetes or early diabetes versus
standard care. An interim review of the data by an independent data
monitoring committee did not show evidence of a signal for
increased cancer risk. Results from the ORIGIN trial are expected
at the end of 2011.

FDA is aware that the manufacturer plans to conduct three
epidemiological studies to further evaluate cancer risk associated
with the use of Lantus. Results from the epidemiological studies
are expected by the end of June 2011.

FDA is also working with the VA to decide whether to use the
VA's patient database to further evaluate any potential cancer risk
with Lantus.

FDA will communicate important new data on this issue when they
become available.